@misc{10498/30352,
year = {2018},
month = {2},
url = {http://hdl.handle.net/10498/30352},
abstract = {The adaptor protein linker for activation of T cells (LAT) has an essential role transducing activatory intracellular signals coming from the TCR/CD3 complex. Previous reports have shown that upon T-cell activation, LAT interacts with the tyrosine kinase Lck, leading to the inhibition of its kinase activity. LAT-Lck interaction seemed to depend on a stretch of negatively charged amino acids in LAT. Here, we have substituted this segment of LAT between amino acids 113 and 126 with a non-charged segment and expressed the mutant LAT (LAT-NIL) in J.CaM2 cells in order to analyze TCR signaling. Substitution of this segment in LAT prevented the activation-induced interaction with Lck. Moreover, cells expressing this mutant form of LAT showed a statistically significant increase of proximal intracellular signals such as phosphorylation of LAT in tyrosine residues 171 and 191, and also enhanced ZAP70 phosphorylation approaching borderline statistical significance (p = 0.051). Nevertheless, downstream signals such as Ca2+ influx or MAPK pathways were partially inhibited. Overall, our data reveal that LAT-Lck interaction constitutes a key element regulating proximal intracellular signals coming from the TCR/CD3 complex.},
organization = {Consejería de Salud de Andalucía, Junta de Andalucía (grants PI-0365-2013 and PI-0055-2017); Instituto de Salud Carlos III (grant PI16-00784 from the “Plan Estatal de I+D+I 2013–2016/FEDER”.},
publisher = {FRONTIERS MEDIA SA},
keywords = {CD3},
keywords = {LAT},
keywords = {Lck},
keywords = {TCR},
keywords = {signaling},
title = {A Stretch of Negatively Charged Amino Acids of Linker for Activation of T-Cell Adaptor Has a Dual Role in T-Cell Antigen Receptor Intracellular Signaling},
doi = {10.3389/fimmu.2018.00115},
author = {Martínez de Arbulo Echevarría, Miguel and Narbona Sánchez,  Isaac and Fernández Ponce, Cecilia Matilde and Vico Barranco, Inmaculada and Rueda-Ygueravide, María Dolores and Dustin, Michael L. and Miazek, Arkadiusz and Durán Ruiz, María del Carmen and García Cózar, Francisco José and Aguado Vidal, Enrique},
}